Quinupristin/dalfopristin

Intravenous, usually 7.5 mg/kg every 8 hours (infections/life threatening VRSA); every 12 hours (skin infections). No renal dosing adjustments, hepatic dosing adjustments are not defined, consider reducing dose.

Quinupristin and dalfopristin are protein synthesis inhibitors in a synergistic manner. While each of the two is only a bacteriostatic agent, the combination shows bactericidal activity.

• Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, and changes the conformation of it, enhancing the binding of quinupristin by a factor of about 100. In addition, it inhibits peptidyl transfer.
• Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide, as well as causing incomplete chains to be released.

Clearance by the liver CYP450:3A4 inhibitor, half-life quinupristin 0.8 hours, dalfopristin 0.7 hours (with persistence of effects for 9-10 hours).

Serious:

1. C.diff-associated diarrhea
2. superinfection
3. anaphylactoid reactions
4. angioedema

Common:

1. Joint aches (arthralgia) or muscle aches (myalgia)
2. Nausea, diarrhea (C. diff associated) or vomiting
3. Rash or itching
4. Headache
5. Hyperbilirubinemia
6. Anemia
7. Thrombophlebitis

The drug inhibits P450 and enhances the effects of terfenadine, astemizole, indinavir, midazolam, calcium channel blockers, warfarin, cisapride and ciclosporin.